What happens at the end of a clinical trial for an investigational neural implant? It may be surprising to learn how difficult it is to answer this question. While new trials are initiated with increasing regularity, relatively little consensus exists on how best to conduct them, and even less on how to ethically end them. The landscape of recent neural implant trials demonstrates wide variability of what happens to research participants after an neural implant trial ends. Some (...) former research participants continue to receive support for their devices (e.g., battery and component replacements, software updates, etc.). Others, when safe, have their neural implants removed through surgical explantation. Still others continue to live with a deactivated neural implant embedded in their body. In the United States, there are no uniform requirements to provide services, of any kind, after an neural implant study ends, and other nations are similarly facing this challenge. The existence of a post-trial gap in an expanding neural implant research ecosystem invites obvious questions: What is owed to neural implant research participants post-trial, and why has providing it been so difficult to accomplish in practice? To take a step forward on this difficult issue, we assembled one group of stakeholders – researchers funded for neuroethics grants by the National Institutes of Health – to explore possible starting points on one topic: ethical guidance for post-trial care of research participants in neural implant trials. Based on shared concerns discussed in the expert workshop the current paper is a call to action. It reports the key areas of convergence from the meeting and highlights important next steps towards developing much needed guidance. (shrink)

Once a neural implant has shown some efficacy during initial research trials, it begins to enter the world of clinical application. This culminates when the implant becomes approved for a particular indication. However, the ethical challenges continue as the technology is adopted as a standard of practice. Patient eligibility criteria, as documented by inclusion and exclusion criteria with any new treatment, are not always clearly quantified and defined. These vagaries can result in considerable debate regarding who should or should (...) not proceed with surgery. There is often considerable room for clinical judgment that can result in extension of the treatment to a wider range of patients. The ethical questions that arise in clinical decisionmaking differ significantly from those inherent in engineering design and research development. (shrink)

Sankary et al. (2022) report the results of an empirical study on research participant experiences of exiting research at the end of clinical trials of deep-brain-stimulation (DBS) and responsive n...

Neurotechnological advancement hinges on cohesive collaboration among diverse stakeholders, all unified in improving user quality of life. However, identifying the specific individuals who should q...

As neural implants transition from engineering design and testing into human subjects research, careful consideration must be paid to the ethical elements in developing research protocols. Although these ethical aspects may be framed by the design choices of the engineering, a number of challenging choices arise. In spite of many ethical considerations for neural implant technologies being shared with generic research ethics questions, there are subsets needing special attention. Even in considerations requiring increased attention, substantial overlap can (...) be found with research ethics questions for general medical implants and for psychiatric pharmaceuticals. The special attention to specific ethical questions in neural implants exists because of the value placed on preserving cognition and control as well as our continued memory of significant past research abuses in neurosurgery. This paper focuses on three issues of particular saliency to neural implant testing: inclusion/exclusion of subjects with psychiatric conditions, consent withdrawal of research subjects, and enhancement as a goal. (shrink)

Gilbert (2015) warns us that advisory brain implant systems—neural implants that predict brain activity and give the user advice based on those predictions—could threaten the user's autonomy. If th...

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a large number of (...) subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. [xx] Stefan Feuerriegel et al., “Causal Machine Learning for Predicting Treatment Outcomes,” Nature Medicine 30, no. 4 (April 2024): 958–68, https://doi.org/10.1038/s41591-024-02902-1. [xxi] Sunderland Baker et al., “Ethical Considerations in Closed Loop Deep Brain Stimulation,” Deep Brain Stimulation 3 (October 1, 2023): 8–15, https://doi.org/10.1016/j.jdbs.2023.11.001. [xxii] David Haslacher et al., “AI for Brain-Computer Interfaces,” 2024, 7, https://doi.org/10.1016/bs.dnb.2024.02.003. [xxiii] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 103–4; “Premarket Approval (PMA),” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026. [xxiv] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 104. [xxv] Burdette and Swartz, 126. [xxvi] Sean L. Metzger et al., “A High-Performance Neuroprosthesis for Speech Decoding and Avatar Control,” Nature 620, no. 7976 (August 2023): 1037–46, https://doi.org/10.1038/s41586-023-06443-4. [xxvii] Hao Fang and Yuxiao Yang, “Predictive Neuromodulation of Cingulo-Frontal Neural Dynamics in Major Depressive Disorder Using a Brain-Computer Interface System: A Simulation Study,” Frontiers in Computational Neuroscience 17 (March 6, 2023), https://doi.org/10.3389/fncom.2023.1119685; Mahsa Malekmohammadi et al., “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease,” Movement Disorders 31, no. 3 (2016): 426–28, https://doi.org/10.1002/mds.26482. [xxviii] Young-Hoon Nho et al., “Responsive Deep Brain Stimulation Guided by Ventral Striatal Electrophysiology of Obsession Durably Ameliorates Compulsion,” Neuron 0, no. 0 (October 20, 2023), https://doi.org/10.1016/j.neuron.2023.09.034. [xxix] Nho et al. [xxx] Nho et al.; Erik Robinson, “Brain Implant at OHSU Successfully Controls Both Seizures and OCD,” OHSU News, accessed March 3, 2024, https://news.ohsu.edu/2023/10/25/brain-implant-at-ohsu-successfully-controls-both-seizures-and-ocd. [xxxi] Awuah et al., “Bridging Minds and Machines”; Haslacher et al., “AI for Brain-Computer Interfaces.” [xxxii] Awuah et al., “Bridging Minds and Machines.” [xxxiii] Sara Green, Barbara Prainsack, and Maya Sabatello, “The Roots of (in)Equity in Precision Medicine: Gaps in the Discourse,” Personalized Medicine 21, no. 1 (January 2024): 5–9, https://doi.org/10.2217/pme-2023-0097. [xxxiv] Green, Prainsack, and Sabatello, 7. [xxxv] Robyn Bluhm and Kirstin Borgerson, “An Epistemic Argument for Research-Practice Integration in Medicine,” The Journal of Medicine and Philosophy: A Forum for Bioethics and Philosophy of Medicine 43, no. 4 (July 9, 2018): 469–84, https://doi.org/10.1093/jmp/jhy009. [xxxvi] Vijay Mahant, “‘Right-to-Try’ Experimental Drugs: An Overview,” Journal of Translational Medicine 18 (June 23, 2020): 253, https://doi.org/10.1186/s12967-020-02427-4. [xxxvii] Michael S. Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

In their article published in Nanoethics, “Ethical, Legal and Social Aspects of Brain-Implants Using Nano-Scale Materials and Techniques”, Berger et al. suggest that there may be a prima facie moral obligation to improve neuro implants with nanotechnology given their possible therapeutic advantages for patients [Nanoethics, 2:241–249]. Although we agree with Berger et al. that developments in nanomedicine hold the potential to render brain implant technologies less invasive and to better target neural stimulation to respond to brain impairments (...) in the near future, we argue against presenting the development of nanobionic clinical devices in terms of a moral obligation to conduct this research. In the first part of the paper, we consider what a duty to pursue new technologies might mean, and in the second we explore some of the negative consequences of defending such development as a moral obligation based on potential benefit. We argue that promoting the advances available to brain implants through developments in nanotechnology and bionics could contribute to medical rhetoric that indirectly increases the risk of exposing patients to harm when participating in clinical trials. We argue that rather than there being a moral obligation to improve nanobionics implants because of their potential benefit, the pursuit of improved neuro implants must be balanced against the prima facie obligations to protect patients against harm and to promote and protect patient autonomy. (shrink)

Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. (...) The animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions. (shrink)

Neural engineering technologies such as implanted deep brain stimulators and brain-computer interfaces represent exciting and potentially transformative tools for improving human health and well-being. Yet their current use and future prospects raise a variety of ethical and philosophical concerns. Devices that alter brain function invite us to think deeply about a range of ethical concerns—identity, normality, authority, responsibility, privacy, and justice. If a device is stimulating my brain while I decide upon an action, am I still the author of (...) the action? Does a device make the interiority of my experience accessible to others? Will the device change the way I think of myself and others think of me? Such fundamental questions arise even when a device is designed for only a relatively circumscribed purpose, such as restoring functioning via a smart prosthetic. We are part of a National Science Foundation-funded Engineering Research Center tasked with investigating philosophical and social implications of neural engineering research and technologies. Neural devices already in clinical use, such as deep brain stimulators for Parkinson's disease or essential tremor, have spurred healthy debate about such implications. Devices currently under development—such as the BrainGate System of implanted brain sensors coupled to robotics in persons with paralysis, exoskeletons for augmented movement, transcranial do-it-yourself stimulators, closed-loop brain stimulating systems, or even brain-to-brain interfacing—promise to extend and deepen these debates. At our center, brain-computer interfaces are the principal focus of work. Even acknowledging that the clinical translation of neural devices and seamless integration by end users may still largely reside in the future, the potential these devices hold calls for careful early analysis. The launching of the Brain Research through Advancing Innovative Neurotechnologies Initiative in April 2013 provides further impetus for this work. (shrink)

We argue that in implanted neurotechnology research, participants and researchers experience what Henry Richardson has called “moral entanglement.” Participants partially entrust researchers with access to their brains and thus to information that would otherwise be private, leading to created intimacies and special obligations of beneficence for researchers and research funding agencies. One of these obligations, we argue, is about continued access to beneficial technology once a trial ends. We make the case for moral entanglement in this context through exploration of (...) participants’ vulnerability, uncompensated risks and burdens, depth of relationship with the research team, and dependence on researchers in implanted neurotechnology trials. (shrink)

Since the development of the first neural prosthesis, that is, the cochlear implant in 1957, neural prosthetics have been one of the highly promising, yet most challenging areas of medicine, while having become a clinically accepted form of invasiveness into the human body. Neural prosthetic devices, of which at least one part is inserted into the body, interact directly with the nervous system to restore or replace lost or damaged sensory, motor, or cognitive functions. This field is (...) not homogenous and encompasses a variety of technologies, which are in various stages of development. Some devices are well established in clinical practice and have become routine, such as cochlear implants. By comparison, other technologies are in experimental phases and still need to be further developed to achieve the desired results. (shrink)

Cochlear implants electrically stimulate surviving auditory neurons in the cochlea to provide severely or profoundly deaf people with access to hearing. Signal processing strategies derive frequency-specific information from the acoustic signal and code amplitude changes in frequency bands onto amplitude changes of current pulses emitted by the tonotopically arranged intracochlear electrodes. This article first describes how parameters of the electrical stimulation influence the loudness evoked and then summarizes two different phenomenological models developed by McKay and colleagues that have been (...) used to explain psychophysical effects of stimulus parameters on loudness, detection, and modulation detection. The Temporal Model is applied to single-electrode stimuli and integrates cochlear neural excitation using a central temporal integration window analogous to that used in models of normal hearing. Perceptual decisions are made using decision criteria applied to the output of the integrator. By fitting the model parameters to a variety of psychophysical data, inferences can be made about how electrical stimulus parameters influence neural excitation in the cochlea. The Detailed Model is applied to multi-electrode stimuli, and includes effects of electrode interaction at a cochlear level and a transform between integrated excitation and specific loudness. The Practical Method of loudness estimation is a simplification of the Detailed Model and can be used to estimate the relative loudness of any multi-electrode pulsatile stimuli without the need to model excitation at the cochlear level. Clinical applications of these models to novel sound processing strategies are described. (shrink)

Background Speech understanding may rely not only on auditory, but also on visual information. Non-invasive functional neuroimaging techniques can expose the neural processes underlying the integration of multisensory processes required for speech understanding in humans. Nevertheless, noise (from fMRI) limits the usefulness in auditory experiments, and electromagnetic artefacts caused by electronic implants worn by subjects can severely distort the scans (EEG, fMRI). Therefore, we assessed audio-visual activation of temporal cortex with a silent, optical neuroimaging technique: functional near-infrared spectroscopy (...) (fNIRS). Methods We studied temporal cortical activation as represented by concentration changes of oxy- and deoxy-hemoglobin in four, easy-to-apply fNIRS optical channels of 33 normal-hearing adult subjects and 5 post-lingually deaf cochlear implant (CI) users in response to supra-threshold unisensory auditory and visual, as well as to congruent auditory-visual speech stimuli. Results Activation effects were not visible from single fNIRS channels. However, by discounting physiological noise through reference channel subtraction, auditory, visual and audiovisual speech stimuli evoked concentration changes for all sensory modalities in both cohorts (p<0.001). Auditory stimulation evoked larger concentration changes than visual stimuli (p<0.001). A saturation effect was observed for the audiovisual condition. Conclusions Physiological, systemic noise can be removed from fNIRS signals by reference channel subtraction. The observed multisensory enhancement of an auditory cortical channel can be plausibly described by a simple addition of the auditory and visual signals with saturation. (shrink)

Revolutions in semiconductor device miniaturization, bioelectronics, and applied neural control technologies are enabling scientists to create machine-assisted minds, science fiction's “cyborgs.” In a paper published in 1999, we sought to draw attention to the advances in prosthetic devices, to the myriad of artificial implants, and to the early developments of this technology in cochlear and retinal implants. Our concern, then and now, was to draw attention to the ethical issues arising from these innovations. Since that time, breakthroughs (...) have occurred at a breathtaking pace. Scientists, researchers, and engineers using differing methodologies are pursuing the possibilities of direct interfaces between brains and machines. Technological innovations as such are neither good nor evil; it is the uses devised for them that create moral implications. As there can be ethical problems inherent in the proper human uses of technologies and because brain chips are a very likely future technology, it is prudent to formulate policies and regulations that will mitigate their ill effects before the technologies are widespread. Unlike genetic technologies, which have received widespread scrutiny within the scientific community, national governments, and international forums, brain–machine interfaces have received little social or ethical scrutiny. However, the potential of this technology to change and significantly affect humans is potentially far greater than that of genetic enhancements, because genetic enhancements are inherently limited by biology and the single location of an individual, whereas hybrids of human and machine are not so restricted. Today, intense interest is focused on the development of drugs to enhance memory; yet, these drugs merely promise an improvement of normal memory, not the encyclopedic recall of a computer-enhanced mind combined with the ability to share information at a distance. The potential of brain chips for transforming humanity are astounding. This paper describes advances in hybrid brain–machine interfaces, offers some likely hypotheses concerning future developments, reflects on the implications of combining cloning and transplanted brain chips, and suggests some potential methods of regulating these technologies. (shrink)

Background: In prior reports, we described the design and initial performance of a fully implantable, bi-directional neural interface system for use in deep brain and other neurostimulation applications. Here we provide an update on the chronic, long-term neural sensing performance of the system using traditional 4-contact leads and extend those results to include directional 8-contact leads.Methods: Seven ovine subjects were implanted with deep brain stimulation leads at different nodes within the Circuit of Papez: four with unilateral leads in (...) the anterior nucleus of the thalamus and hippocampus; two with bilateral fornix leads, and one with bilateral hippocampal leads. The leads were connected to either an Activa PC+S® or Percept PC°ledR deep brain stimulation and recording device. Spontaneous local field potentials, evoked potentials, LFP response to stimulation, and electrode impedances were monitored chronically for periods of up to five years in these subjects.Results: The morphology, amplitude, and latencies of chronic hippocampal EPs evoked by thalamic stimulation remained stable over the duration of the study. Similarly, LFPs showed consistent spectral peaks with expected variation in absolute magnitude dependent upon behavioral state and other factors, but no systematic degradation of signal quality over time. Electrode impedances remained within expected ranges with little variation following an initial stabilization period. Coupled neural activity between the two nodes within the Papez circuit could be observed in synchronized recordings up to 5 years post-implant. The magnitude of passive LFP power recorded from directional electrode segments was indicative of the contacts that produced the greatest stimulation-induced changes in LFP power within the Papez network.Conclusion: The implanted device performed as designed, providing the ability to chronically stimulate and record neural activity within this network for up to 5 years of follow-up. (shrink)

Brain–Computer Interface research is an interdisciplinary area of study within Neural Engineering. Recent interest in end-user perspectives has led to an intersection with user-centered design. The goal of user-centered design is to reduce the translational gap between researchers and potential end users. However, while qualitative studies have been conducted with end users of BCI technology, little is known about individual BCI researchers’ experience with and attitudes towards UCD. Given the scientific, financial, and ethical imperatives of UCD, we sought to (...) gain a better understanding of practical and principled considerations for researchers who engage with end users. We conducted a qualitative interview case study with neural engineering researchers at a center dedicated to the creation of BCIs. Our analysis generated five themes common across interviews. The thematic analysis shows that participants identify multiple beneficiaries of their work, including other researchers, clinicians working with devices, device end users, and families and caregivers of device users. Participants value experience with device end users, and personal experience is the most meaningful type of interaction. They welcome end-user input, but are skeptical of limited focus groups and case studies. They also recognize a tension between creating sophisticated devices and developing technology that will meet user needs. Finally, interviewees espouse functional, assistive goals for their technology, but describe uncertainty in what degree of function is “good enough” for individual end users. Based on these results, we offer preliminary recommendations for conducting future UCD studies in BCI and neural engineering. (shrink)

Information and communication technologies , with their increasing and widespread utilization in daily life, may exert an important impact on brain performances. The development of their use for improving several cerebral processes, by abolishing the brain/machine interface, is envisaged and is subject to debate. The scientific research on brain implants and brain gene transfer aiming to restore central nervous system functions, altered by disease or trauma, may contribute to this debate. Indeed, the advances that are enabling non drug-mediated approaches (...) for direct interventions on the brain are raising the possibility not only of restoring neural functions for therapeutic purposes, but also of monitoring, controlling and ultimately modifying from the outside these functions for enhancement. This paper gives an overview of the state of the art of brain implants and brain gene transfer for neurological diseases with a particular emphasis on Parkinson’s disease and a forecast on their possible application for other conditions. In doing so, the authors, who are neuroscientists working in the field of gene transfer for neuropsychiatric diseases, aim to establish a scientifically, medically and technically realistic framework to open up discussion on relevant ethical issues in this domain. (shrink)

Recent advances in wireless data transmission technology have the potential to revolutionize clinical neuroscience. Today sensing-capable electrical stimulators, known as “bidirectional devices”, are used to acquire chronic brain activity from humans in natural environments. However, with wireless transmission come potential failures in data transmission, and not all available devices correctly account for missing data or provide precise timing for when data losses occur. Our inability to precisely reconstruct time-domain neural signals makes it difficult to apply subsequent neural signal (...) processing techniques and analyses. Here, our goal was to accurately reconstruct time-domain neural signals impacted by data loss during wireless transmission. Towards this end, we developed a method termed Periodic Estimation of Lost Packets. PELP leverages the highly periodic nature of stimulation artifacts to precisely determine when data losses occur. Using simulated stimulation waveforms added to human EEG data, we show that PELP is robust to a range of stimulation waveforms and noise characteristics. Then, we applied PELP to local field potential recordings collected using an implantable, bidirectional DBS platform operating at various telemetry bandwidths. By effectively accounting for the timing of missing data, PELP enables the analysis of neural time series data collected via wireless transmission—a prerequisite for better understanding the brain-behavior relationships underlying neurological and psychiatric disorders. (shrink)

As cognitive neuroscience has advanced, the list of prospective internal, biological enhancements has steadily expanded. Education and training, as well as the use of external information‐processing devices, may be labeled as “conventional” means of cognition enhancement (CE). They are often well established and culturally accepted. By contrast, methods of enhancing cognition through “unconventional” means, such as ones involving deliberately created nootropic drugs, gene therapy, or neural implants, are nearly all to be regarded as experimental at the present time. (...) Transcranial magnetic stimulation (TMS), genetic interventions, brain‐computer interfaces and new senses are highly experimental and unlikely to be important over the next 15 years. Many of the concerns about enhancement are nonspecific to the tools used to achieve it, which means that enhancement–ethic scrutiny should also apply to nonbiological external enhancements. (shrink)

Deep Brain Stimulation (DBS) represents a key area of neuromodulation that has gained wide adoption for the treatment of neurological and experimental testing for psychiatric disorders. It is associated with specific therapeutic effects based on the precision of an evolving mechanistic neuroscientific understanding. At the same time, there are obstacles to achieving symptom relief because of the incompleteness of such an understanding. These obstacles are at least in part based on the complexity of neuropsychiatric disorders and the incompleteness of DBS (...) devices to represent prosthetics that modulate the breadth of pathological processes implicated in these disorders. Neuroprostheses, such as an implanted DBS system, can have vast effects on subjects in addition to the specific neuropsychiatric changes they are intended to produce. These effects largely represent blind spots in the current debate on neuromodulation. Anthropological accounts can illustrate the broad existential dimensions of patients’ illness and responses to neural implants. In combination with current neuroscientific understanding, neuropsychiatric anthropology may illuminate the possibilities and limits of neurodevices as technical “world enablers”. (shrink)

This book is a critical examination of the philosophical and moral issues in relation to human enhancement and the various related medical developments that are now rapidly moving from the laboratory into the clinical realm. In the book, the author critically examines technologies such as genetic engineering, neural implants, pharmacologic enhancement, and cryonic suspension from transhumanist and bioconservative positions, focusing primarily on moral issues and what it means to be a human in a setting where technological interventions sometimes (...) impact strongly on our humanity. The author also introduces the notion that death is a process rather than an event, as well as identifies philosophical and clinical limitations in the contemporary determination of brain death as a precursor to organ procurement for transplantation. The discussion on what exactly it means to be dead is later applied to explore philosophical and clinical issues germane to the cryonics movement. Written by a physician/ scientist and heavily referenced to the peer-reviewed medical and scientific literature, the book is aimed at advanced students and academics but should be readable by any intelligent reader willing to carry out some side-reading. No prior knowledge of moral philosophy is assumed, as the various key approaches to moral philosophy are outlined early in the book. (shrink)

There is a growing recognition that the ongoing use of investigational neural implants requires continued access to clinical expertise and specialized healthcare (e.g., Hendriks et al., 2019). Howe...

The possibility of enhancing human abilities often raises public concern about equality and social impact. This chapter aims at one particular group of technologies, cognitive enhancement, and one particular fear, that enhancement will create social divisions and possibly expanding inequalities. The chapter argues that cognitive enhancements could offer significant social and economic benefits. The basic forms of internal cognitive enhancement technologies foreseen today are pharmacological modifications, genetic interventions, transcranial magnetic stimulation, and neural implants. Cognitive enhancements can influence the (...) economy through reduction of losses, individual economic benefits, and society‐wide benefits. The strongest objection to the introduction of any enhancement technology is that it will create inequality, injustice, and unfairness. While there are clear economic and social benefits to cognitive enhancement, there exist anumber of obstacles to its development and use. One obstacle is the present system for licensing drugs and medical treatments. (shrink)

Utilising science and technology to maximize human performance is often an essential feature of military activity. This can often be focused on mission success rather than just the welfare of the individuals involved. This tension has the potential to threaten the autonomy of soldiers and military physicians around the taking or administering of enhancement neurotechnologies (e.g., pills, neural implants, and neuroprostheses). The Hybrid Framework was proposed by academic researchers working in the U.S. context and comprises “rules” for military (...) neuroenhancement (e.g., ensuring transparency and maintaining dignity of the warfighter). Integrating traditional bioethical perspectives with the unique requirements of the military environment, it has been referenced by military/government agencies tasked with writing official ethical frameworks. Our two-part investigation explored the ethical dimensions of military neuroenhancements with military officers – those most likely to be making decisions in this area in the future. In three workshops, structured around the Hybrid Framework, we explored what they thought about the ethical issues of enhancement neurotechnologies. From these findings, we conducted a survey (N = 332) to probe the extent of rule endorsement. Results show high levels of endorsement for a warfighter’s decision-making autonomy, but lower support for the view that enhanced warfighters would pose a danger to society after service. By examining the endorsement of concrete decision-making guidelines, we provide an overview of how military officers might, in practice, resolve tensions between competing values or higher-level principles. Our results suggest that the military context demands a recontextualisation of the relationship between military and civilian ethics. (shrink)

Recent developments in neuroscience create new opportunities for understanding the human brain. The power to do good, however, is also the power to harm, so scientific advances inevitably foster as many dystopian fears as utopian hopes. For instance, neuroscience lends itself to the fear that people will be forced to reveal thoughts and feelings which they would not have chosen to reveal, and of which they may be unaware. It also lends itself to the worry that people will be encouraged (...) to submit to medication or surgery which, even if otherwise beneficial, alters their brain in ways that undermine their identity and agency. As Kenneth Foster notes, neural implants can have surprising and unintended adverse effects, even when they help to mitigate the loss of bodily control associated with Parkinson’s disease, or help to provide hearing for children who would otherwise be profoundly deaf. While the risk of adverse outcomes are scarcely specific to neuroscience, he thinks that ‘These issues are perhaps more acute’ with the latter than with other medical interventions, ‘because they are intimately and fundamentally related to a person’s communication with the outside world’. [ 2006 196] -/- Neuroscience, like genomic science, then, is likely to create new ways of harming people. Many of these will involve violations of privacy. However, these are unlikely fundamentally to challenge the reasons to value privacy, or our ability to protect it in the foreseeable future. Rather, I would suggest, the major threat to privacy comes from the difficulty of determining its nature and value and when, if ever, efforts to protect it are justified. So I will start by examining some threats to privacy, and their implications for neuroscience, before turning to philosophical problems in understanding the nature and value of privacy, and the practical consequences of those philosophical difficulties. (shrink)

This chapter examines how advances in nanotechnology might impact criminal sentencing. While many scholars have considered the ethical implications of emerging technologies, such as nanotechnology, few have considered their potential impact on crucial institutions such as our criminal justice system. Specifically, I will discuss the implications of two types of technological advances for criminal sentencing: advanced tracking devices enabled by nanotechnology, and nano-neuroscience, including neural implants. The key justifications for criminal punishment- including incapacitation, deterrence, rehabilitation, and retribution – (...) apply very differently to criminal sentences using these emerging technologies than they do to imprisonment. Further, use of these technologies would represent a shift away from retribution as the primary justification for criminal punishment. In addition, the possibility of nano-neural implants entails a new model of rehabilitation: namely, involuntary rehabilitation aimed at changing an offender’s character, rather than his environment. (shrink)

“Archangel” explores the consequences of Marie's over‐parenting of her daughter, Sara, through the use of a neural implant (the Archangel) that allows Marie to track (and block) Sara's experiences. In attempting to fulfill her duty to protect Sara, Marie ultimately fails morally as a parent. What is fascinating is that different schools of philosophical thought – contemporary liberal philosophy, ancient Greek Aristotelian ethics, contemporary feminist ethics of care, and contemporary Wittgensteinian ethics – all reach the same conclusion about Marie's (...) moral failure, while teasing out different strands of this failure. (shrink)

This chapter contains sections titled: General Ethical Issues Cellular, Genetic and Tissue Engineering Biomaterials, Prostheses and Implants Biomedical Imaging and Optics Neural Engineering References and Further Reading.

This book begins well. Blank first gives, for the benefit of lay readers and those unfamiliar with the area of neuroscience, a brief but informative description of the structure and workings of the brain itself. He then goes on to offer an overview of the current state of brain intervention ranging from direct brain intervention (electroconvulsive therapy, electronic and magnetic stimulation, psychosurgery and neural implants), psychotropic drugs, the use of virtual reality, nootropics and neurogenetics. Blank offers a concise (...) summary and evaluation of each of these methods, outlining both potential benefits and risks. He makes the important point that most of these methods, however, do not present a cure, but rather are aimed at altering behaviour, raising the important question as the ethics of behavioural control for social convenience – particularly in relation to the vulnerable, such as the management of children with ADHD.Blank then offers a well-researched and balanced overview .. (shrink)

Neural devices have the capacity to enable users to regain abilities lost due to disease or injury – for instance, a deep brain stimulator (DBS) that allows a person with Parkinson’s disease to regain the ability to fluently perform movements or a Brain Computer Interface (BCI) that enables a person with spinal cord injury to control a robotic arm. While users recognize and appreciate the technologies’ capacity to maintain or restore their capabilities, the neuroethics literature is replete with examples (...) of concerns expressed about agentive capacities: A perceived lack of control over the movement of a robotic arm might result in an altered sense of feeling responsible for that movement. Clinicians or researchers being able to record and access detailed information of a person’s brain might raise privacy concerns. A disconnect between previous, current, and future understandings of the self might result in a sense of alienation. The ability to receive and interpret sensory feedback might change whether someone trusts the implanted device or themselves. Inquiries into the nature of these concerns and how to mitigate them has produced scholarship that often emphasizes one issue – responsibility, privacy, authenticity, or trust – selectively. However, we believe that examining these ethical dimensions separately fails to capture a key aspect of the experience of living with a neural device. In exploring their interrelations, we argue that their mutual significance for neuroethical research can be adequately captured if they are described under a unified heading of agency. On these grounds, we propose an “Agency Map” which brings together the diverse neuroethical dimensions and their interrelations into a comprehensive framework. With this, we offer a theoretically-grounded approach to understanding how these various dimensions are interwoven in an individual’s experience of agency. (shrink)

Implantable brain-computer interfaces are being developed to restore speech capacity for those who are unable to speak. Patients with locked-in syndrome or amyotrophic lateral sclerosis could be able to use covert speech – vividly imagining saying something without actual vocalisation – to trigger neural controlled systems capable of synthesising speech. User control has been identified as particularly pressing for this type of BCI. The incorporation of machine learning and statistical language models into the decoding process introduces a contribution to (...) the output that is beyond the user’s control. Whilst this type of ‘shared control’ of BCI action is not unique to speech BCIs, the automated shaping of what a user ‘says’ has a particularly acute ethical dimension, which may differ from parallel concerns surrounding automation in movement BCIs. This paper provides an analysis of the control afforded to the user of a speech BCI of the sort under development, as well as the relationships between accuracy, control, and the user’s ownership of the speech produced. Through comparing speech BCIs with BCIs for movement, we argue that, whilst goal selection is the more significant locus of control for the user of a movement BCI, control over process will be more significant for the user of the speech BCI. The design of the speech BCI may therefore have to trade off some possible efficiency gains afforded by automation in order to preserve sufficient guidance control necessary for users to express themselves in ways they prefer. We consider the implications for the speech BCI user’s responsibility for produced outputs and their ownership of token outputs. We argue that these are distinct assessments. Ownership of synthetic speech concerns whether the content of the output sufficiently represents the user, rather than their morally relevant, causal role in producing that output. (shrink)

Bidirectional deep brain stimulation (DBS) platforms have enabled a surge in hours of recordings in naturalistic environments, allowing further insight into neurological and psychiatric disease states. However, high amplitude, high frequency stimulation generates artifacts that contaminate neural signals and hinder our ability to interpret the data. This is especially true in psychiatric disorders, for which high amplitude stimulation is commonly applied to deep brain structures where the native neural activity is miniscule in comparison. Here, we characterized artifact sources (...) in recordings from a bidirectional DBS platform, the Medtronic Summit RC + S, with the goal of optimizing recording configurations to improve signal to noise ratio (SNR). Data were collected from three subjects in a clinical trial of DBS for obsessive-compulsive disorder. Stimulation was provided bilaterally to the ventral capsule/ventral striatum (VC/VS) using two independent implantable neurostimulators. We first manipulated DBS amplitude within safe limits (2–5.3 mA) to characterize the impact of stimulation artifacts on neural recordings. We found that high amplitude stimulation produces slew overflow, defined as exceeding the rate of change that the analog to digital converter can accurately measure. Overflow led to expanded spectral distortion of the stimulation artifact, with a six fold increase in the bandwidth of the 150.6 Hz stimulation artifact from 147–153 to 140–180 Hz. By increasing sense blank values during high amplitude stimulation, we reduced overflow by as much as 30% and improved artifact distortion, reducing the bandwidth from 140–180 Hz artifact to 147–153 Hz. We also identified artifacts that shifted in frequency through modulation of telemetry parameters. We found that telemetry ratio changes led to predictable shifts in the center-frequencies of the associated artifacts, allowing us to proactively shift the artifacts outside of our frequency range of interest. Overall, the artifact characterization methods and results described here enable increased data interpretability and unconstrained biomarker exploration using data collected from bidirectional DBS devices. (shrink)

Advancing neuroscience is one of many topics that pose a challenge often called “the alignment problem”—the challenge, that is, of assuring that science policy is responsive to and in some sense squares with the public's values. This issue of the Hastings Center Report launches a series of scholarly essays and articles on the ethical and social issues raised by this vast body of medical research and bench science. The series, which will run under the banner “Neuroscience and Society,” is supported (...) by the Dana Foundation and seeks to promote deliberative public engagement, broadly understood, about neuroscience. As a social goal, deliberative public engagement is both ubiquitous and elusive—called for everywhere yet difficult to undertake at a national level on a complex scientific topic. To be meaningful, deliberative public engagement must occur in many locations in a society and be carried forward by many actors. Scholarly writing might contribute in several ways. (shrink)

Cerebral organoid models in-of-themselves are considered as an alternative to research animal models. But their developmental and biological limitations currently inhibit the probability that organoids can fully replace animal models. Furthermore, these organoid limitations have, somewhat ironically, brought researchers back to the animal model via xenotransplantation, thus creating hybrids and chimeras. In addition to attempting to study and overcome cerebral organoid limitations, transplanting cerebral organoids into animal models brings an opportunity to observe behavioral changes in the animal itself. Traditional animal (...) ethics frameworks, such as the well-known three Rs (reduce, refine, and replace), have previously addressed chimeras and xenotransplantation of tissue. But these frameworks have yet to completely assess the neural-chimeric possibilities. And while the three Rs framework was a historical landmark in animal ethics, there are identifiable gaps in the framework that require attention. The authors propose to utilize an expanded three Rs framework initially developed by David DeGrazia and Tom L. Beauchamp, known as the Six Principles (6Ps). This framework aims to expand upon the three Rs, fill in the gaps, and be a practical means for assessing animal ethical issues like that of neural-chimeras and cerebral organoid xenotransplantation. The scope of this 6Ps application will focus on two separate but recent studies, which were published in 2019 and 2020. First, they consider a study wherein cerebral organoids were grown from donors with Down syndrome and from neurotypical donors. After these organoids were grown and studied, they were then surgically implanted into mouse models to observe the physiological effects and any behavioral change in the chimera. Second, they consider a separate study wherein neurotypical human embryonic stem cell-derived cerebral organoids were grown and transplanted into mouse and macaque models. The aim was to observe if such a transplantation method would contribute to therapies for brain injury or stroke. The authors place both studies under the lens of the 6Ps framework, assess the relevant contexts of each case, and provide relevant normative conclusions. In this way, they demonstrate how the 6Ps could be applied in future cases of neural-chimeras and cerebral organoid xenotransplantation. (shrink)

As clinical trials end, little is understood about how participants exiting from clinical trials approach decisions related to the removal or post-trial use of investigational brain implants, such as deep brain stimulation (DBS) devices. This empirical bioethics study examines how research participants experience the process of exit from research at the end of clinical trials of implanted neural devices. Using a modified grounded theory study design, we conducted semi-structured, in-depth interviews with 16 former research participants from clinical trials (...) of DBS and responsive neurostimulation (RNS). Open-ended questions elicited motivations for joining the trial, understanding of study procedures at the time of initial informed consent, the process of exiting from research, and decisions about device removal or post-trial device use. Thematic analysis identified categories related to: limited preparedness for the end of research participation, straightforwardness of decisions to explant or keep the device, reconciling with the end of research participation, reconciling post-trial expectations, and achieving a sense of closure after exit from research. A preliminary theoretical model describes contextual factors influencing the process and experience of exit from research. Experiences of clinical trial participants should guide research practices to enhance the ethical design and conduct of clinical trials in DBS and other brain devices. (shrink)

DBS Think Tank IX was held on August 25–27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers can freely discuss current and emerging deep brain stimulation technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in (...) its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year’s meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury. (shrink)

Within psychology and the brain sciences, the study of consciousness and its relation to human information processing is once more a focus for productive research. However, some ancient puzzles about the nature of consciousness appear to be resistant to current empirical investigations, suggesting the need for a fundamentally different approach. In Velmans I have argued that functional accounts of the mind do not `contain' consciousness within their workings. Investigations of information processing are not investigations of consciousness as such. Given this, (...) first-person investigations of experience need to be related nonreductively to third-person investigations of processing. For example, conscious contents may be related to neural/physical representations via a dual-aspect theory of information. Chalmers arrives at similar conclusions. But there are also theoretical differences. Unlike Chalmers I argue for the use of neutral information processing language for functional accounts rather than the term `awareness'. I do not agree that functionalctional equivalence cannot be extricated from phenomenal equivalence, and suggest a hypothetical experiment for doing so - using a cortical implant for blindsight. I argue that not all information has phenomenal accompaniments, and introduce a different form of dual-aspect theory involving `psychological complementarity'. I also suggest that the hard problem posed by `qualia' has its origin in a misdescription of everyday experience implicit in dualism. (shrink)

Deep brain stimulation (DBS) of the globus pallidus interna and subthalamic nucleus has restored some degree of motor control in many patients in advanced stages of Parkinson’s disease. DBS has also been used to treat dystonia, essential tremor (progressive neurological condition causing trembling), chronic pain, obsessive-compulsive disorder, Tourette’s syndrome, major depressive disorder, obesity, cerebral palsy, and the minimally conscious state. Although the underlying mechanisms of the technique are still not clear, DBS can modulate underactive or overactive neural circuits and (...) restore disrupted communication between and among groups of neurons in interacting regions of the brain. This can control and relieve many symptoms associated with a range of neurological and psychiatric disorders.But the procedures of implanting and stimulating the electrodes are brain-invasive and entail significant risks. Some patients receiving DBS have experienced intracerebral hemorrhage, infection, cognitive disturbances such as impulsive behavior, and affective disturbances such as mania. It is not known whether continuous electrical stimulation of the brain would reshape synaptic connectivity and permanently alter neural circuits in ways that may not be salutary. The risk of these effects indicates that DBS should be used only when a patient’s condition is refractory to all other interventions and when there is a high probability that the technique will benefit the patient and improve his or her quality of life. If a patient’s quality of life is poor and all other treatment options have been exhausted, then the likelihood of benefit can justify physicians’ exposing patients to some risk. The clinical and ethical significance of the risk in DBS underscores the obligation of physicians to obtain fully informed consent from patients undergoing the procedure. (shrink)

Power density spectra and phase synchrony measurements were taken from intracranial electrode grids implanted in epileptic subjects. Comparisons were made between data from the waking state and from the period of unconsciousness immediately following a generalised tonic–clonic seizure. Power spectra in the waking state resembled coloured noise. Power spectra in the unconscious state resembled coloured noise from 1 to about 5 Hz, but at higher frequencies changed in two out of three subjects to resemble white noise. This boosted unconscious gamma (...) power to a higher level than conscious gamma power. For both gamma and beta passbands, synchrony measurements showed more widespread phase synchrony in the unconscious than the conscious state. We conclude that neither gamma activity per se nor phase synchrony per se are neural correlates of consciousness. (shrink)

No agreement exists among ethical theories on what cancount as a right moral motivation. This hampers us from knowingwhether an intervention in motivation biology can be considered positivefor human morality. To overcome this difficulty, this paper identifiesminimal requirements for moral enhancement that could be accepted bythe major moral theories. Subsequently four possible scenarios are presentedwhere the most promising neural interventions on moral motivationare implemented, by means of drugs, electromagnetic stimulation ofbrain, or biotechnological brain implants. The ultimate goal of (...) this paperis to evaluate the results of each one of these interventions according totheir capacity to fulfill the identified requirements. (shrink)

BackgroundThe therapeutic effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) is related to the modulation of pathological neural activities, particularly the synchronization in the β band (13–35 Hz). However, whether the local β activity in the STN region can directly predict the stimulation outcome remains unclear.ObjectiveWe tested the hypothesis that low-β (13–20 Hz) and/or high-β (20–35 Hz) band activities recorded from the STN region can predict DBS efficacy.MethodsLocal field potentials (LFPs) were recorded (...) in 26 patients undergoing deep brain stimulation surgery in the subthalamic nucleus area. Recordings were made after the implantation of the DBS electrode prior to its connection to a stimulator. The maximum normalized powers in the theta (4–7 Hz), alpha (7–13 Hz), low-β (13–20 Hz), high-β (20–35 Hz), and low-γ (40–55 Hz) subbands in the postoperatively recorded LFP were correlated with the stimulation-induced improvement in contralateral tremor or bradykinesia–rigidity. The distance between the contact selected for stimulation and the contact with the maximum subband power was correlated with the stimulation efficacy. Following the identification of the potential predictors by the significant correlations, a multiple regression analysis was performed to evaluate their effect on the outcome.ResultsThe maximum high-β power was positively correlated with bradykinesia–rigidity improvement (rs = 0.549, p < 0.0001). The distance to the contact with maximum high-β power was negatively correlated with bradykinesia–rigidity improvement (rs = −0.452, p < 0.001). No significant correlation was observed with low-β power. The maximum high-β power and the distance to the contact with maximum high-β power were both significant predictors for bradykinesia–rigidity improvement in the multiple regression analysis, explaining 37.4% of the variance altogether. Tremor improvement was not significantly correlated with any frequency.ConclusionHigh-β oscillations, but not low-β oscillations, recorded from the STN region with the DBS lead can inform stimulation-induced improvement in contralateral bradykinesia–rigidity in patients with PD. High-β oscillations can help refine electrode targeting and inform contact selection for DBS therapy. (shrink)

This article describes two features of technoscience, which are significant for the consideration of the prospects of human improvement projects. The first feature of technoscience is that the object of its research is artificial in origin which means created by person. As an example of new objects, situations and problems are given projects to create «designer children», development of transplantation, creating implantable neural interface. The second feature of technoscience is that the well-established methods can't be applied to determine the (...) results of the implementation of human improvement projects. As an example, the article discussed neo-eugenics projects. The article concludes that today in the social sciences there is no clear position on the grounds of human improvement projects. However, this is not an obstacle for the development of technoscience. (shrink)

Rationale: Deep brain stimulation (DBS) of the hippocampus is proposed for enhancement of memory impaired by injury or disease. Many pre-clinical DBS paradigms can be addressed in epilepsy patients undergoing intracranial monitoring for seizure localization, since they already have electrodes implanted in brain areas of interest. Even though epilepsy is usually not a memory disorder targeted by DBS, the studies can nevertheless model other memory-impacting disorders, such as Traumatic Brain Injury (TBI). Methods: Human patients undergoing Phase II invasive monitoring for (...) intractable epilepsy were implanted with depth electrodes capable of recording neurophysiological signals. Subjects performed a delayed-match-to-sample (DMS) memory task while hippocampal ensembles from CA1 and CA3 cell layers were recorded to estimate a multi-input, multi-output (MIMO) model of CA3-to-CA1 neural encoding and a memory decoding model (MDM) to decode memory information from CA3 and CA1 neuronal signals. After model estimation, subjects again performed the DMS task while either MIMO-based or MDM-based patterned stimulation was delivered to CA1 electrode sites during the encoding phase of the DMS trials. Each subject was sorted (post hoc) by prior experience of repeated and/or mild-to-moderate brain injury (RMBI), TBI, or no history (control) and scored for percentage successful delayed recognition (DR) recall on stimulated vs. non-stimulated DMS trials. The subject’s medical history was unknown to the experimenters until after individual subject memory retention results were scored. Results: When examined compared to control subjects, both TBI and RMBI subjects showed increased memory retention in response to both MIMO and MDM-based hippocampal stimulation. Furthermore, effects of stimulation were also greater in subjects who were evaluated as having pre-existing mild-to-moderate memory impairment. Conclusion: These results show that hippocampal stimulation for memory facilitation was more beneficial for subjects who had previously suffered a brain injury (other than epilepsy), compared to control (epilepsy) subjects who had not suffered a brain injury. This study demonstrates that the epilepsy/intracranial recording model can be extended to test the ability of DBS to restore memory function in subjects who previously suffered a brain injury other than epilepsy, and support further investigation into the beneficial effect of DBS in TBI patients. (shrink)

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the (...) field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank. (shrink)

The loss or absence of vision is probably one of the most incapacitating events that can befall a human being. The importance of vision for humans is also reflected in brain anatomy as approximately one third of the human brain is devoted to vision. It is therefore unsurprising that throughout history many attempts have been undertaken to develop devices aiming at substituting for a missing visual capacity. In this review, we present two concepts that have been prevalent over the last (...) two decades. The first concept is sensory substitution, which refers to the use of another sensory modality to perform a task that is normally primarily sub-served by the lost sense. The second concept is cross-modal plasticity, which occurs when loss of input in one sensory modality leads to reorganization in brain representation of other sensory modalities. Both phenomena are training-dependent. We also briefly describe the history of blindness from ancient times to modernity, and then proceed to address themeansthat have been used to help blind individuals, with an emphasis on modern technologies, invasive (various type of surgical implants) and non-invasive devices. With the advent of brain imaging, it has become possible to peer into the neural substrates of sensory substitution and highlight the magnitude of the plastic processes that lead to a rewired brain. Finally, we will address the important question of the value and practicality of the available technologies and future directions. (shrink)

Enhancing cognition is a complex activity, for the sake of which humanity has developed a rich array of techniques and skills. We can distinguish between three categories: a) cognitive supports and education; b) neural cognitive enhancers: drugs and other ways to improve the functionality of cognitive neural networks; c) technological cognitive enhancers: implants, extended minds and technological supports variously integrated in the neural cognitive networks. Applying a version of the Parity Principle, I argue that there is (...) no morally relevant difference in the three categories. What we want to preserve while using these techniques is not the biological status quo of the mind of persons, but rather personal identities. In this perspective, there can be no general objection to cognitive enhancement. Every technique, even very traditional ones, have their drawbacks, especially when they threaten to reduce the autonomy of agents in moulding their own personal identity. (shrink)